Addressing threats to health care's core values, especially those stemming from concentration and abuse of power. Advocating for accountability, integrity, transparency, honesty and ethics in leadership and governance of health care.

Sunday, July 18, 2010

The Avandia Spin Cycle Continues Even After the FDA Safety Hearings

We have posted multiple times about Avandia (rosiglitazone), GlaxoSmithKline's star-crossed glucose-lowering drug. While Avandia has received considerable media coverage, we focused on two questions: 1 - what are the benefits and harms of rosiglitazone as a treatment of type 2 diabetes, and therefore for which patients under what circumstances should this drug be used? 2 - what barriers have prevented physicians and patients from getting the best possible answer to the first question, and what can be done about them? (See recent post here.)

In particular, the Avandia case has illustrated how those with vested interests in the success of a health care product have done their best to obscure information that might threaten its success, even when doing so obscures the information that physicians and patients need to make the best possible decisions. At one point, (in 2007, no less) we called this the "Avandia spin cycle."

Avandia once again has been in the news after the US Food and Drug Administration's hearings on the safety of the drug. These hearings were so well covered in the media that a lengthy summary would be superfluous. However, their main points demonstrated the persistence of the Avandia spin cycle:
- An FDA reviewer felt that "the company's misreadings of the ... Record trial ... were so profound, he concluded, that they 'suggest serious flaws with trial conduct.'" (per Gardiner Harris writing in the New York Times)
-A former FDA reviewer "withheld from regulators a study showing its Avandia diabetes drug may cause heart attacks." (per Bloomberg News)
- GlaxoSmithKline's forerunner SmithKline Beecham "secretly began a study to find out if its diabetes medicine, Avandia, was safer for the heart than a competing pill, Actos, made by Takeda." However, "the study also provided clear signs that it [Avandia] was riskier to the heart. But instead of publishing the results, the company spent the next 11 years trying to cover them up." (per Gardiner Harris writing in the New York Times.
- "Government experts and a panel of medical advisers repeatedly voiced skepticism on Tuesday about the trustworthiness of GlaxoSmithKline, which makes the controversial diabetes drug Avandia." (per Gardiner Harris again writing in the New York Times.)

So the Avandia saga has brought to the front pages the concerns we have had with suppression and manipulation of clinical research, especially when pursued by health care organizations with vested interests in the results of specific research projects coming out a certain way, and how they have been enabled by those with conflicts of interest. Doctors thus should be worried whether those of us who try to practice evidence-based medicine have been fooled into practicing pseudo-evidence-based-medicine.

Those commenting on the story focused on the need for transparency when clinical research is funded and run by the corporations whose products are being evaluated.
- "GlaxoSmithKline, the maker of Avandia, can't be trusted to report adverse clinical results fairly. The company must be watched like a hawk as additional trials that it sponsors go forward." (NY Times editorial)
- "What America should demand in return for ... [generous patent] protection is that the FDA be able to make an honest evaluation of the efficacy of drugs. When drug companies make this impossible by suppressing test results, not only do they violate their fundamental obligation of honesty with the public, their customers and their regulator, but they also break the bargain they have struck in return for the protection of their intellectual capital." (Former NY Attorney General Eliot Spitzer in Slate.)

Instead, as I have written before, maybe we ought to consider whether those with vested interests in drugs or devices ought to be running clinical research meant to evaluate their own products.

Ironically, while this discussion of how the Avandia spin cycle first began to revolve were going on, others were still trying to add revolutions (per minute). In particular, a Reuters story noted:

Three influential groups of doctors who treat diabetes urged patients not to stop taking Avandia, saying on Thursday that while news about the controversial drug may be frightening, it would be worse to suddenly stop taking it.

That is odd, given that Avandia has never been shown to improve clinical outcomes for patients with diabetes, and that there are many other drugs that control blood sugar which appear to be safer. But wait, there is more,

The Endocrine Society, American Diabetes Association and the American Association of Clinical Endocrinologists worried that patients may be afraid to take Avandia.

'Patients should continue taking all currently prescribed medications unless instructed otherwise by their health care provider,' Dr. Robert Vigersky of the Endocrine Society said in a statement.

'Stopping diabetes medications can cause significant harm and result in higher levels of blood glucose that may cause severe short term health problems and could increase the risk of diabetes-related complications in the long term.'

Would not it make more sense to advise patients still on Avandia to consult with their doctors urgently about possible alternatives? Meanwhile, it does not seem irrational to be afraid of taking Avandia, given the increasing evidence about its harms, and increasing evidence that what we know about its harms may be an under-estimate.

So I wondered why these august medical societies seemed so unaffected about the doubts about Avandia's safety, and about the evidence offered to support its use that the latest news ought to generate. It turns out that all three of the medical societies get financial support from, -- wait for it --, GlaxoSmithKline.

The Endocrine Society lists GSK as one of its Corporate Liaison Board Members. The American Diabetes Association lists GSK as one of its Banting Circle Supporters, that is, those that give at least $1,000,000 a year. The American Association of Clinical Endocrinologists lists GSK as a member of its Corporate AACE Partnership. (I was not able to find out the total amount contributed by GSK to either the Endocrine Society or the AACE.)

So once again, the loudest voices in support of the product come from those used to, and perhaps dependent on financial support from its manufacturer. As a physician, I have been particularly disappointed that our medical societies, whose missions are ostensibly to support our professional values, seem to act more and more like marketers for the companies whose contributions, rather than members' dues increasingly support them.

The cycle keeps spinning.

For further thoughts on the latest in the Avandia case, see this post by Howard Brody on the Hooked: Ethics, Medicine and Pharma blog, and this by Alison Bass on the Alison Bass Blog.

5 comments:

Bill
said...

I certainly share your concern about the purposeful obscuring of drug studies by those who stand to make a profit. The influence of power and money on the safety of our medicine is one of the largest challenges facing our health care system. There are some great interviews with doctors, reformers and legislatures concerning the vital need for honest evidence based medicine at http://www.ourblook.com/topic/healthcare.html which I have found useful on these subjects. You or your readers might want to check it out.

There is certainly something to be said for not having pharmaceutical companies conducting their own clinical trials, but the issue is that the alternatives are highly problematic. If you move toward a clinical trials being performed by a third party such as another business, collusion is sure to occur sooner or later as the drug makers find those companies that are more 'expedient' and less rigorous in conducting the trials. At the same time, having a government body conduct the trials will be met with serious opposition on the basis of poor government expediency. It is not that its not doable, it would just take serious effort. In any case, I suspect we will sadly be living with companies playing these games for a number of years to come.

I, too, have been astonished by the "Avandia spin cycle" (as you so correctly put it). The FDA seems to have the best interest of big money and big drug companies at heart, rather than the consumer (who it was established to protect). It's little wonder that it's illegal to say eating oranges can "cure" scurvey. Oranges can't be patented, so there is no money in natural vitamin C. This is a great blog and information for consumers. Thanks!

Bill brings up an excellent point about the inherent conflict of interest that exists in having medical reviews conducts by professionals who have a financial claim to a drug company. Hopefully when the FDA's official decision comes out in a few weeks we will see something being done about the way drugs are approved in general. Here is an article that explains what is at stake... http://www.dgmslaw.com/blog/bid/41231/FDA-July-Review-of-Avandia-Carries-Significant-Importance

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